caa a22 4500 44586110X CHVBK 20180317145443.0 cr unu---uuuuu 170323e20111101xx s 000 0 eng 10.1007/s00439-011-0989-6 doi (NATIONALLICENCE)springer-10.1007/s00439-011-0989-6 Linkage analysis of plasma dopamine β-hydroxylase activity in families of patients with schizophrenia [Elektronische Daten] [Joseph Cubells, Xiangqing Sun, Wenbiao Li, Robert Bonsall, John McGrath, Dimitri Avramopoulos, Virginia Lasseter, Paula Wolyniec, Yi-Lang Tang, Kristina Mercer, Ann Pulver, Robert Elston] Dopamine β-hydroxylase (DβH) catalyzes the conversion of dopamine to norepinephrine. DβH enters the plasma after vesicular release from sympathetic neurons and the adrenal medulla. Plasma DβH activity (pDβH) varies widely among individuals, and genetic inheritance regulates that variation. Linkage studies suggested strong linkage of pDβH to ABO on 9q34, and positive evidence for linkage to the complement fixation locus on 19p13.2-13.3. Subsequent association studies strongly supported DBH, which maps adjacent to ABO, as the locus regulating a large proportion of the heritable variation in pDβH. Prior studies have suggested that variation in pDβH, or genetic variants at DβH, associate with differences in expression of psychotic symptoms in patients with schizophrenia and other idiopathic or drug-induced brain disorders, suggesting that DBH might be a genetic modifier of psychotic symptoms. As a first step toward investigating that hypothesis, we performed linkage analysis on pDβH in patients with schizophrenia and their relatives. The results strongly confirm linkage of markers at DBH to pDβH under several models (maximum multipoint LOD score, 6.33), but find no evidence to support linkage anywhere on chromosome 19. Accounting for the contributions to the linkage signal of three SNPs at DBH, rs1611115, rs1611122, and rs6271 reduced but did not eliminate the linkage peak, whereas accounting for all SNPs near DBH eliminated the signal entirely. Analysis of markers genome-wide uncovered positive evidence for linkage between markers at chromosome 20p12 (multi-point LOD=3.1 at 27.2cM). The present results provide the first direct evidence for linkage between DBH and pDβH, suggest that rs1611115, rs1611122, rs6271 and additional unidentified variants at or near DBH contribute to the genetic regulation of pDβH, and suggest that a locus near 20p12 also influences pDβH. Springer-Verlag, 2011 Cubells Joseph Department of Human Genetics, Emory University School of Medicine, 30322, Atlanta, GA, USA aut Sun Xiangqing Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, 44106, Cleveland, OH, USA aut Li Wenbiao Department of Human Genetics, Emory University School of Medicine, 30322, Atlanta, GA, USA aut Bonsall Robert Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 30322, Atlanta, GA, USA aut McGrath John Department of Psychiatry, Johns Hopkins School of Medicine, 21231, Baltimore, MD, USA aut Avramopoulos Dimitri Department of Psychiatry, Johns Hopkins School of Medicine, 21231, Baltimore, MD, USA aut Lasseter Virginia Department of Psychiatry, Johns Hopkins School of Medicine, 21231, Baltimore, MD, USA aut Wolyniec Paula Department of Psychiatry, Johns Hopkins School of Medicine, 21231, Baltimore, MD, USA aut Tang Yi-Lang Department of Human Genetics, Emory University School of Medicine, 30322, Atlanta, GA, USA aut Mercer Kristina Department of Human Genetics, Emory University School of Medicine, 30322, Atlanta, GA, USA aut Pulver Ann Department of Psychiatry, Johns Hopkins School of Medicine, 21231, Baltimore, MD, USA aut Elston Robert Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, 44106, Cleveland, OH, USA aut Human Genetics Springer-Verlag 130/5(2011-11-01), 635-643 0340-6717 130:5<635 2011 130 439 https://doi.org/10.1007/s00439-011-0989-6 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00439-011-0989-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Cubells Joseph Department of Human Genetics, Emory University School of Medicine, 30322, Atlanta, GA, USA aut NATIONALLICENCE 700 1- Sun Xiangqing Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, 44106, Cleveland, OH, USA aut NATIONALLICENCE 700 1- Li Wenbiao Department of Human Genetics, Emory University School of Medicine, 30322, Atlanta, GA, USA aut NATIONALLICENCE 700 1- Bonsall Robert Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, 30322, Atlanta, GA, USA aut NATIONALLICENCE 700 1- McGrath John Department of Psychiatry, Johns Hopkins School of Medicine, 21231, Baltimore, MD, USA aut NATIONALLICENCE 700 1- Avramopoulos Dimitri Department of Psychiatry, Johns Hopkins School of Medicine, 21231, Baltimore, MD, USA aut NATIONALLICENCE 700 1- Lasseter Virginia Department of Psychiatry, Johns Hopkins School of Medicine, 21231, Baltimore, MD, USA aut NATIONALLICENCE 700 1- Wolyniec Paula Department of Psychiatry, Johns Hopkins School of Medicine, 21231, Baltimore, MD, USA aut NATIONALLICENCE 700 1- Tang Yi-Lang Department of Human Genetics, Emory University School of Medicine, 30322, Atlanta, GA, USA aut NATIONALLICENCE 700 1- Mercer Kristina Department of Human Genetics, Emory University School of Medicine, 30322, Atlanta, GA, USA aut NATIONALLICENCE 700 1- Pulver Ann Department of Psychiatry, Johns Hopkins School of Medicine, 21231, Baltimore, MD, USA aut NATIONALLICENCE 700 1- Elston Robert Department of Epidemiology and Biostatistics, Case Western Reserve University School of Medicine, 44106, Cleveland, OH, USA aut NATIONALLICENCE 773 0- Human Genetics Springer-Verlag 130/5(2011-11-01), 635-643 0340-6717 130:5<635 2011 130 439 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer